Pulmonary vagal afferents provide some of the most important breathing control inputs to the respiratory center. However, the structure of vagal receptors is not yet well known. Lack of an available and effective method to identify pulmonary receptors is the major limiting factor. Here we describe a new approach using confocal microscopy to examine the structure of immunohistochemically stained airway receptors by using Na(+)/K(+)-ATPase as a marker. This method permits detailed observation of pulmonary receptor structures and their relationship to target tissue in the rabbit. The parent axon has multiple branches that supply the receptor structure. Each structure has multiple endings that form leaf-like terminals. This technique permits examining pulmonary receptor structures in detail, and should assist in identifying the morphology of the receptors and the mechanisms of receptor activation.
Animals ; Biomarkers ; analysis ; Bronchi ; innervation ; Immunohistochemistry ; methods ; Mechanoreceptors ; physiology ; Neuroepithelial Bodies ; physiology ; Rabbits ; Respiratory System ; innervation ; Sodium-Potassium-Exchanging ATPase ; analysis

Information on the morphology of airway receptors is limited. The present study surveys rabbit airway receptors using immunohistochemical and fluorescent labeling to identify their structure with confocal microscopy. Various receptor types were observed to have multiple branches where a parent axon fed several structures. Receptors were located in different layers of the airway, i.e., smooth muscle, lamina propria (submucosa) and the epithelium. Smooth muscle and submucosal receptors were innervated by thick myelinated fibers, while epithelial receptors were supplied by thin-diameter axons. Structures of smooth muscle receptors and some submucosal receptors covered a relatively large area, while epithelial receptors were less extended. In addition, intrapulmonary ganglia were also labeled. Some were closely associated with the axons of smooth muscle receptors.
Animals ; Axons ; ultrastructure ; Bronchi ; ultrastructure ; Epithelium ; ultrastructure ; Mechanoreceptors ; diagnostic imaging ; Microscopy, Confocal ; Muscle, Smooth ; ultrastructure ; Rabbits ; Respiratory System ; ultrastructure ; Sensory Receptor Cells ; ultrastructure ; Trachea ; ultrastructure ; Ultrasonography ; Vagus Nerve ; ultrastructure

Arachidonic acid (AA) in the cell membrane produces a variety of metabolites by different enzymatic pathways. These lipid metabolites, along with other mediators, play an important role in the inflammatory processes. Many of them can bind directly to the receptors on the sensory endings and initiate electrical impulses to be transmitted to the central nervous system, causing reflex responses. These bioactive AA metabolites may also alter the lung mechanics (mechanical environment of the sensory ending), and in turn, stimulate sensory afferents. In addition, some metabolites may sensitize the sensory endings and make them more responsive to other mechanical or chemical stimulation. These metabolites may also induce other mediators and modulators to cause physiological effects. Furthermore, some of them may attract inflammatory cells to produce a localized effect. In short, AA metabolites may come from different sources and act through multiple pathways to stimulate airway sensors. This brief review is intended to illustrate the underlying mechanisms and help elucidate the inflammatory process in the airways.
Animals ; Arachidonic Acid ; metabolism ; Humans ; Inflammation ; physiopathology ; Respiratory Physiological Phenomena ; Respiratory System ; metabolism ; Sensory Receptor Cells ; physiology ; Vagus Nerve ; physiology

Breathing is critically depending on a variety of sensory feedbacks from multiple sources for its optimal performance. The sensory information from the lung and airways probably provides one of the most important feedbacks to adjust the respiratory controller to generate optimal breathing movements. Since Breuer and Hering made the seminal report regarding role of the vagus nerve in control of breathing in 1868, airway sensory receptors have been a subject for intensive and extensive studies. After more than a century investigation, our knowledge accumulates immensely, however, our understanding of the nature of these sensory receptors is still far from complete. This brief review provides an overview on this topic.
Humans ; Lung ; innervation ; physiology ; Mechanoreceptors ; physiology ; Neuroepithelial Bodies ; physiology ; Pulmonary Stretch Receptors ; physiology ; Reflex ; physiology ; Respiratory System ; innervation ; Vagus Nerve ; physiology

Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces slowly adapting pulmonary stretch receptors (SARs) to discharge paradoxically. Paradoxical discharge is characterized by increased SAR activity during lung deflation coupled with silence during lung inflation. We hypothesized that over-excitation silences the SARs. Accordingly, if cyclic inflation pressure was reduced so as to lower SAR stimulation, paradoxical discharge would be prevented. In the present study, single-unit activity of SARs was recorded in anesthetized, open-chest and mechanically ventilated rabbits with positive-end-expiratory pressure (PEEP). After microinjection of ouabain into the receptive field, SAR activity initially increased and then gradually became paradoxical. During paradoxical cycling, SAR activity started and stopped abruptly, oscillating between high frequency discharge during lung deflation and silence during peak inflation. Removing PEEP reduced basal cyclic stimulation and returned the discharge pattern to normal, that is, SAR activity was highest at peak inflation pressure but silent during deflation. It is speculated that stretching SARs causes Na(+) influx, producing generator potential (GP). Normally, GP recovers by Na(+) extrusion via Na(+)/K(+)-ATPase. Ouabain inhibits the ATPase, which limits Na(+) extrusion, and thus sustains the GP. Therefore, after ouabain microinjection, lung inflation will further increase GP, causing over-excitation to silence the SARs.
Action Potentials ; physiology ; Adaptation, Physiological ; drug effects ; Animals ; Lung ; drug effects ; physiology ; Male ; Mechanoreceptors ; physiology ; Ouabain ; pharmacology ; Pulmonary Stretch Receptors ; drug effects ; physiology ; Pulmonary Ventilation ; drug effects ; physiology ; Rabbits ; Sodium-Potassium-Exchanging ATPase ; antagonists & inhibitors ; physiology ; Vagus Nerve ; physiology

Lung cancer is a major medical problem. Despite advances in molecular biology and pharmacology, the outcome of lung cancer treatment is unsatisfactory. Clinically, inflammation and cancer are closely associated, and, genetically, these two processes are regulated by the same gene loci. Inflammation promotes cancer formation. Increasing evidence shows that neuroimmune interaction involving inflammatory disease and the vagus nerves are crucial in the interaction. Airway sensory receptors are biosensors that detect the lung inflammatory process through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the extent and intensity of inflammation. Tumor cells express receptors for neurotransmitters and provide a substrate for direct interaction with neurons. Thus, neural regulation of the immune response is targeted towards inflammation as well as tumors. The airway sensors can detect cancer-related cytokines, which provides a direct pathway to inform the brain of tumor growth. The knowledge of how these sensors may monitor tumor progression and provide neuroimmune interaction in the control of tumor development and metastasis will improve our treatment of lung cancer.
Carcinogenesis ; Cytokines ; physiology ; Humans ; Inflammation ; pathology ; Lung ; innervation ; pathology ; Lung Neoplasms ; pathology ; Sensory Receptor Cells ; physiology ; Vagus Nerve ; physiology

The Academy of Medicine (AMS) and Ministry of Health (MOH) have developed the clinical practice guidelines on Assessment and Management of Infertility at Primary Healthcare Level to provide doctors and patients in Singapore with evidence-based treatment for infertility. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the AMS-MOH clinical practice guidelines on Assessment and Management of Infertility at Primary Healthcare Level, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical/2013/cpgmed_infertility.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.
Evidence-Based Medicine ; Female ; Guidelines as Topic ; Humans ; Infertility ; diagnosis ; therapy ; Male ; Practice Guidelines as Topic ; Primary Health Care ; methods ; standards ; Public Health ; standards ; Singapore